This project is a prospective test of an in vitro - in vivo scaling model that can be used to predict the occurrence of pharmacokinetic drug interactions in humans on the basis of in vitro data from microsomal preparations of human liver The index compound will be midazolam, a substrate for Cytochrome P450-3A4, and the metabolic inhibitor will be the azole antifungal agent ketoconazole. In vitro studies will establish the quantitative activity of ketoconazole as an inhibitor of biotransformation of midazolam to its hydroxylated metabolites.